Modulation of AMPA Receptors by TARPs (transmembrane AMPA Receptor regulatory Proteins)

TARP-ProjektAMPA receptors are a subfamily of ionotropic glutamate receptors and play a crucial role in fast signal transduction in the brain. Although AMPA receptors can exert their basic function, i.e., fluxing ions into the cell upon binding of glutamate, on their own, many other proteins are involved in the fine tuning of this process. Most of these proteins are important for transporting the AMPA receptors to their correct destination when they are needed, but also for removing them when they are not needed any more. The discovery of a family of six small membrane proteins that are also involved in this regulation of transport, but in addition directly change the functional properties of AMPA receptors, was a surprising achievement. In particular, these transmembrane AMPA receptor regulatory proteins (TARPs) boost the glutamate-induced signal by increasing the opening time of the AMPA receptor channel. To understand the function of AMPA receptors, it is important to understand this mechanism. We are particularly interested in characterising the different impacts of the different TARPs on AMPA receptors and investigate the interactions that form the basis of this differential modulation.


Project-Related Publications

  • C.Sager, D. Tapken, and M. Hollmann (2010).
    The C-terminal domains of TARPs: Unexpectedly versatile domains.
    Channels 4(3): 155-158.
    doi: 10.4161/chan.4.3.11349
    Abstract
     
  • C. Sager, J. Terhag, S. Kott, and M. Hollmann (2009).
    C-terminal domains of transmembrane α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor regulatory proteins not only facilitate trafficking but are major modulators of AMPA receptor function.
    Journal of Biological Chemistry 284(47): 32413-32424.
    doi: 10.1074/jbc.M109.039891
    Abstract
     
  • S. Kott, C. Sager, D. Tapken, M. Werner, and M. Hollmann (2009).
    Comparative analysis of the pharmacology of GluR1 in complex with TARPs γ2, γ3, γ4, and γ8.
    Neuroscience 158(1): 78-88 (Special issue “Protein Trafficking, Targeting, and Interaction at the Glutamate Synapse”).
    doi: 10.1016/j.neuroscience.2007.12.047
    Abstract
     
  • C. Sager, D. Tapken, S. Kott, and M. Hollmann (2009).
    Functional modulation of AMPA receptors by transmembrane AMPA receptor regulatory proteins.
    Neuroscience 158(1): 45-54 (Special issue “Protein Trafficking, Targeting, and Interaction at the Glutamate Synapse”).
    doi: 10.1016/j.neuroscience.2007.12.046
    Abstract
     
  • C. Körber, M. Werner, S. Kott, Z.-L. Ma, and M. Hollmann (2007).
    The transmembrane AMPA receptor regulatory protein γ4 is a more effective modulator of AMPA receptor function than stargazin (γ2).
    Journal of Neuroscience 27(31): 8442-8447.
    doi: 10.1523/jneurosci.0424-07.2007
    Abstract
     
  • C. Körber, M. Werner, J. Hoffmann, C. Sager, M. Tietze, S.M. Schmid, S. Kott, and M. Hollmann (2007).
    Stargazin interaction with α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors is critically dependent on the amino acid at the narrow constriction of the ion channel.
    Journal of Biological Chemistry 282(26): 18758-18766.
    doi: 10.1074/jbc.M611182200
    Abstract
     
  • S. Kott, M. Werner, C. Körber, and M. Hollmann (2007).
    Electrophysiological properties of AMPA receptors are differentially modulated depending on the associated member of the TARP family.
    Journal of Neuroscience 27(14): 3780-3789.
    doi: 10.1523/jneurosci.4185-06.2007
    Abstract      Pressemitteilung
     

Project-Related Doctoral Theses

Project-Related Master Theses

  • Christoph Körber
    Modulation of the electrophysiological properties of AMPA receptors by TARPs
    01.03.2006 to 27.09.2006
     
  • Charlotte Sager
    Characterisation of the differential modulation of AMPA receptors by TARPs
    01.03.2006 to 31.08.2006
     

Project-Related Bachelor Theses

  • Alina Dressler
    The role of the Ex1 domain of stargazin in the modulation of AMPA receptor function
    05.10.2009
     
  • Ellen Kloosterboer
    Generation and characterization of truncated stargazin proteins
    01.10.2009
     
  • Markus Sudbrock
    Cloning of an AMPA receptor-stargazin fusion protein and its expression in Xenopus oocytes
    11.08.2005
     
  • Romy Marx
    The effect of stargazin on the expression of the glutamate receptor GluR1(Q)flip
    23.06.2004
     

Scientists Involved

Sandra LemosSandra Lemos
Room NC 6/167
Tel. +49 234 32-28240
E-mail


Simon KöstersSimon Kösters
Room NC 6/131
Tel. +49 234 32-27496
E-mail


Peer Henning HöckerPeer Henning Höcker
Room NC 6/131
Tel. +49 234 32-27496
E-mail


Charlotte SagerDr. Charlotte Sager
At the department until 2010
E-mail


Sabine KottDr. Sabine Kott
At the department until 2010
E-mail


Markus WernerDr. Markus Werner
At the department until 2008
Currently Department of Cell Physiology, RUB
E-mail


Christoph KörberChristoph Körber
At the department until 2007
Currently University of Heidelberg
E-mail